RABIES VACCINE--Skin Pigmentation Reaction - YorkieTalk.com Forums

Kris Christine · 02-25-2008, 05:40 AM

Because "Post-rabies vaccination alopecia is most commonly seen in toy or small breeds," I wanted to post this in case anyone's Yorkie has experienced this particular reaction to rabies vaccination.

PERMISSION GRANTED TO CROSS-POST THIS MESSAGE.

--------------------------------------------------------------------------------
Ischemic Dermatopathy / Cutaneous vasculitis

A little known and often misdiagnosed reaction to the rabies vaccine in dogs, this problem may develop near or over the vaccine administration site and around the vaccine material that was injected, or as a more widespread reaction. Symptoms include ulcers, scabs, darkening of the skin, lumps at the vaccine site, and scarring with loss of hair. In addition to the vaccination site, lesions most often develop on the ear flaps (pinnae), on the elbows and hocks, in the center of the footpads and on the face. Scarring may be permanent. Dogs do not usually seem ill, but may develop fever. Symptoms may show up within weeks of vaccination, or may take months to develop noticeably.

Dogs with active lesion development and / or widespread disease may be treated with pentoxyfylline, a drug that is useful in small vessel vasculitis, or tacrolimus, an ointment that will help suppress the inflammation in the affected areas.

Owners and veterinarians of dogs who have developed this type of reaction should review the vaccination protocol critically and try to reduce future vaccinations to the extent medically and legally possible. At the very least, vaccines from the same manufacturer should be avoided. It is also recommended that the location in which future vaccinations are administered should be changed to the rear leg, as far down on the leg as possible and should be given in the muscle rather than under the skin.

http://en.wikipedia.org/wiki/Vaccination_of_dogs
--------------------------------------------------------------------------------

A retrospective study of canine and feline cutaneous vasculitis
Patrick R. Nichols**Animal Allergy and Dermatology Center of Central Texas, 4434 Frontier Trail, Austin, Texas 78745, USA
Daniel O. Morris††Department of Clinical Studies, Veterinary Hospital, University of Pennsylvania, 3850 Spruce St., Philadelphia, Pennsylvania 19104, USA and
Karin M. Beale‡‡Gulf Coast Veterinary Dermatology and Allergy, 1111 West Loop South, Suite 120, Houston, Texas 77027, USA
*Animal Allergy and Dermatology Center of Central Texas, 4434 Frontier Trail, Austin, Texas 78745, USA †Department of Clinical Studies, Veterinary Hospital, University of Pennsylvania, 3850 Spruce St., Philadelphia, Pennsylvania 19104, USA ‡Gulf Coast Veterinary Dermatology and Allergy, 1111 West Loop South, Suite 120, Houston, Texas 77027, USA
Correspondence: Daniel O. Morris, Department of Clinical Studies, Veterinary Hospital, University of Pennsylvania, 3850 Spruce St., Philadelphia, PA 19104, USA. E-mail:domorris@vet.upenn.edu
Abstract

Twenty-one cases of cutaneous vasculitis in small animals (dogs and cats) were reviewed, and cases were divided by clinical signs into five groups. An attempt was made to correlate clinical types of vasculitis with histological inflammatory patterns, response to therapeutic drugs and prognosis. Greater than 50% of the cases were idiopathic, whereas five were induced by rabies vaccine, two were associated with hypersensitivity to beef, one was associated with lymphosarcoma and two were associated with the administration of oral drugs (ivermectin and itraconazole). Only the cases of rabies vaccine-induced vasculitis in dogs had a consistent histological inflammatory pattern (mononuclear/nonleukocytoclastic) and were responsive to combination therapy with prednisone and pentoxifylline, or to prednisone alone. Most cases with neutrophilic or neutrophilic/eosinophilic inflammatory patterns histologically did not respond to pentoxifylline, but responded to sulfone/sulfonamide drugs, prednisone, or a combination of the two.

http://www.blackwell-synergy.com/doi...3.2001.00268.x
--------------------------------------------------------------------------------
Vitale, Gross, Magro (1999)
Vaccine-induced ischemic dermatopathy in the dog
Veterinary Dermatology 10 (2), 131–142.
doi:10.1046/j.1365-3164.1999.00131.x

Prev Article Next Article
Full Article
Vaccine-induced ischemic dermatopathy in the dog
Vitale,
Gross &
Magro
1Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, California 95616, USA, 2IDDEX Veterinary Services, California Dermatopathology Service, 2825 KOVR Drive, West Sacramento, California 95605, USA, 3Department of Pathology, Beth Israel Hospital, Harvard Medical School, Pathology Services, Inc., 640 Memorial Drive, Cambridge, Massuchusetts 02139, USA
Correspondence to: Carlo B. Vitale
Present address: Encina Veterinary Hospital, 2803 Ygnacio Valley Road, Walnut Creek, California 94598, USA.
Abstract
Post-rabies vaccination alopecia associated with concurrent multifocal ischemic dermatopathy was identified in three unrelated dogs. All dogs received subcutaneous rabies vaccine dorsally between the scapulae several months prior to observation of the initial area of alopecia at the vaccination site. All three dogs developed multifocal cutaneous disease within 1–5 months after the appearance of the initial skin lesion. Cutaneous lesions were characterized clinically by variable alopecia, crusting, hyperpigmentation, erosions, and ulcers on the pinnal margins, periocular areas, skin overlying boney prominences, tip of the tail, and paw pads. Lingual erosions and ulcers were observed in two dogs. Histopathologic examination of the skin revealed moderate to severe follicular atrophy, hyalinization of collagen, vasculopathy, and cell-poor interface dermatitis and mural folliculitis. Hypovascularity was demonstrated by diminished Factor VIII staining of blood vessels. Nodular accumulations of lymphocytes, plasma cells, and histiocytes in the deep dermis and panniculus also were noted at the rabies vaccination site. An atrophic, ischemic myopathy paralleling the onset of skin disease was identified in two dogs. Histological examination of muscle biopsy specimens demonstrated perifascicular atrophy, perimysial fibrosis, and complement (C) 5b-9 (membrane attack complex) deposition in the microvasculature of both dogs with myopathy. Marked improvement of the skin disease was obtained with oral pentoxifylline and vitamin E.

http://www.blackwell-synergy.com/doi...4.1999.00131.x

--------------------------------------------------------------------------------
The Armed Forces Institute of Pathology
Department of Veterinary Pathology
WEDNESDAY SLIDE CONFERENCE
2002-2003

CONFERENCE 19
26 February 2003

Conference Moderator:
Dr. Michael Goldschmidt, MSc, BVMS, MRCVS Diplomate, ACVP
Professor, School of Veterinary Medicine
University of Pennsylvania
Philadelphia, PA 19104-6051

CASE II - 2513-02 (AFIP 2839301)

Signalment: 5-year-old, male, castrated, canine, Chihuahua
History: One by three cm lesion on the dorso-lateral neck
Gross Pathology: None
03WSC19 - 2 -
Laboratory Results: None

Contributor’s Morphologic Diagnosis: Post-rabies vaccination alopecia with injection site granuloma and panniculitis

Contributor’s Comment: The hair follicles are markedly atretic and their lower portions are replaced by an eosinophilic, hyaline stroma. The deeper dermis also has a cleft or seroma pocket that is partially lined by a thin layer of foamy macrophages and multinucleated giant cells with more peripheral lymphoid nodules with many scattered dermal macrophages, lymphocytes and plasma cells. Scattered melanin-laden macrophages (positive with Fontana-Masson melanin stain and negative for hemosiderin with a Prussian blue stain) are in the hyalinized lengths of the hair follicles with a few beneath the epidermal basement membrane (pigmentary incontinence).

This is post-rabies vaccination alopecia with an underlying injection site granuloma. Post-rabies vaccination alopecia is most commonly seen in toy or small breeds, especially Poodles, but Chihuahua cases have been reported. The lesion usually develops three to six months after vaccination.

Other reports describe mild to severe lymphocytic inflammation with macrophages in the superficial or deep dermis or scattered around hair follicle remnants. The dermis may have smudging of the collagen, especially around the hair follicles. Rabies vaccine antigen has been found in the hair follicle epithelium and in the walls of vessels in the area. One report of focal alopecia developing in all twelve of twelve inbred miniature Poodles injected with a killed rabies vaccine two months earlier suggest that there may be a familial predisposition to this apparently idiosyncratic, hypersensitivity reaction to the antigen.

http://www.afip.org/vetpath/WSC/wsc02/02wsc19.pdf

CONTINUED ON NEXT POST

Kris Christine · 02-25-2008, 05:41 AM

This is a continuation of the previous post which was too long.

--------------------------------------------------------------------------------
Pentoxifylline (Trental)

Pentoxifylline, sold by Hoechst-Roussel under the trade name Trental®, is a methylxanthine derivative that decreases platelet activation, inhibits T- and B-lymphocyte activation, and decreases natural killer cell activity. In humans, it is used for down-regulating inflammatory conditions, such as granuloma anulare, scleroderma, and even spider bites. In veterinary medicine, it is most useful in cases involving some degree of vasculopathy, such as dermatomyositis, vasculitis, rabies vaccine-induced alopecia, and mucinosis. Since it may decease scarring, it is sometimes even used long term in cases of acral lick dermatitis. It is also sometimes used for the treatment of inhalant allergies, allergic bronchitis, and pattern alopecias.

With pentoxifylline, it may take 1-3 months before the benefits of treatment are evident. Gastrointestinal upset, either vomiting, diarrhea (or both) is the most likely adverse effect, although thrombocytopenia has also been reported. There have actually been relatively few side effects reported with the drug.

Tacrolimus (Protopic)

Tacrolimus is an inhibitor of T-lymphocyte activation. It is at least 10 times as potent as cyclosporine, yet is minimally absorbed through the skin. Tacrolimus is available commercially as a 0.1% topical, and as a 0.03% pediatric formulation (Protopic: Fugisawa), in 30 g and 60 g tubes. It is licensed for the treatment of eczematous dermatitis in people.

Tacrolimus has been used for the treatment of cutaneous lupus erythematosus, and also for the eczematous manifestations of inhalant allergies. It is typically applied twice daily for a trial period of 6-8 weeks. Once remission is achieved, it may be possible to taper to once daily, and sometimes even alternate-day therapy.

There are a few cautions to use, even though major side effects have not been reported. There is some mild to moderate burning at the site of application, at least reported in people. It is important that only a thin film be applied to the skin, and that the product is not ingested. Sun exposure is typically restricted for the first hour or two after application.

PENTOXIFYLLINE

Pentoxifylline is a methylxanthine derivative first used and marketed in the United States for intermittent claudication in humans. Hypercoagulable states and blood flow abnormalities improve through decreased platelet aggregation and adhesion, increased red cell deformability, decreased vasoconstriction, increased plasminogen activator, increased plasmin, increased antithrombin III, decreased fibrinogen, decreased alpha2-antiplasmin, decreased alpha1-antitrypsin, and decreased alpha2-macroglobulin. Results of subsequent studies revealed that the drug results in a variety of physiologic changes at the cellular level. Immune modulation includes increased leukocyte deformability, decreased leukocyte adhesion and aggregation, decreased neutrophil superoxide release, decreased neutrophil degranulation, increased leukocyte chemotaxis, decreased monocyte TNF-alpha production, decreased leukocyte response to TNF-alpha, decreased production and leukocyte response to IL-1 and IL-12, increased production of IL-10 and PGE2, and decreased natural killer cell activity. Many of these effects result in inhibition of T- and B-cell activation. Wound healing and connective tissue disorders are improved by increased fibroblast collagenases, decreased fibroblast collagen, decreased fibroblast fibronectin, decreased fibroblast glycosaminoglycans, and decreased response to TNF-alpha. Based on these experimental findings, pentoxifylline has been used for a wide variety of diseases in humans. Adverse effects are rare over a wide dosage range, up to 2200 mg/day, and are minimized using sustained-release tablets. Adverse effects include nausea, vomiting, dizziness, and headache, all seen in less than 3% of human patients. Drug interactions have been reported with cisplatin, alkylating agents, and amphotericin B. Cimetidine increases the level of pentoxifylline by decreasing its clearance. Synergistic activity has been reported between pentoxifylline and ciprofloxacin in the inhibition of TNF-alpha.

Recent pharmacokinetic studies suggest that pentoxifylline should be administered every 8 hours in dogs and that administration with food does not affect absorption into the systemic circulation. Pentoxifylline has been used for a wide variety of cutaneous disorders in dogs. They include dermatomyositis, vasculitis, rabies vaccine induced vasculitis, vascular thrombosis leading to ear margin necrosis, wounds, acral lick dermatitis, and diseases resulting in severe fibrosis such as deep scarring pyoderma. Variable efficacy has been anecdotally reported for these diseases but no specific cases or controlled studies have been published. Efficacy has been well-documented for the ability of pentoxifylline (Trental, Hoechst Marion Roussel, 10 mg/kg, q12h, PO) to prevent allergic contact reactions to plants of the Commelinceae family in three dogs. Response was seen after only 2 days of treatment with relapse occurring upon discontinuation of the drug in one dog. No adverse effects were observed in the three dogs. A double-blind placebo-controlled study was conducted to evaluate pentoxifylline for the treatment of canine atopic dermatitis. Ten dogs were administered the drug at 10 mg/kg, q12h, PO for 4 weeks. Pruritus and erythema significantly decreased in the dogs administered the test drug versus those on placebo. However, most of the dogs still had residual pruritus at 4 weeks. Increasing the dosage and frequency may increase efficacy. Pentoxifylline is available in 400 mg controlled-release tablets. The optimal dosage and duration of pentoxifylline administration are not known for all of the various indications in dogs. For small dogs, the large tablets are reformulated into capsules. Pentoxifylline causes GI irritancy so should not be reformulated as a liquid and should be administered with a small amount of food.

02-25-2008, 05:40 AM	#1
Kris Christine YT Addict Join Date: Jan 2008 Location: THE RABIES CHALLENGE FUND Posts: 434	RABIES VACCINE--Skin Pigmentation Reaction Because "Post-rabies vaccination alopecia is most commonly seen in toy or small breeds," I wanted to post this in case anyone's Yorkie has experienced this particular reaction to rabies vaccination. PERMISSION GRANTED TO CROSS-POST THIS MESSAGE. -------------------------------------------------------------------------------- Ischemic Dermatopathy / Cutaneous vasculitis A little known and often misdiagnosed reaction to the rabies vaccine in dogs, this problem may develop near or over the vaccine administration site and around the vaccine material that was injected, or as a more widespread reaction. Symptoms include ulcers, scabs, darkening of the skin, lumps at the vaccine site, and scarring with loss of hair. In addition to the vaccination site, lesions most often develop on the ear flaps (pinnae), on the elbows and hocks, in the center of the footpads and on the face. Scarring may be permanent. Dogs do not usually seem ill, but may develop fever. Symptoms may show up within weeks of vaccination, or may take months to develop noticeably. Dogs with active lesion development and / or widespread disease may be treated with pentoxyfylline, a drug that is useful in small vessel vasculitis, or tacrolimus, an ointment that will help suppress the inflammation in the affected areas. Owners and veterinarians of dogs who have developed this type of reaction should review the vaccination protocol critically and try to reduce future vaccinations to the extent medically and legally possible. At the very least, vaccines from the same manufacturer should be avoided. It is also recommended that the location in which future vaccinations are administered should be changed to the rear leg, as far down on the leg as possible and should be given in the muscle rather than under the skin. http://en.wikipedia.org/wiki/Vaccination_of_dogs -------------------------------------------------------------------------------- A retrospective study of canine and feline cutaneous vasculitis Patrick R. Nichols*Animal Allergy and Dermatology Center of Central Texas, 4434 Frontier Trail, Austin, Texas 78745, USA Daniel O. Morris††Department of Clinical Studies, Veterinary Hospital, University of Pennsylvania, 3850 Spruce St., Philadelphia, Pennsylvania 19104, USA and Karin M. Beale‡‡Gulf Coast Veterinary Dermatology and Allergy, 1111 West Loop South, Suite 120, Houston, Texas 77027, USA Animal Allergy and Dermatology Center of Central Texas, 4434 Frontier Trail, Austin, Texas 78745, USA †Department of Clinical Studies, Veterinary Hospital, University of Pennsylvania, 3850 Spruce St., Philadelphia, Pennsylvania 19104, USA ‡Gulf Coast Veterinary Dermatology and Allergy, 1111 West Loop South, Suite 120, Houston, Texas 77027, USA Correspondence: Daniel O. Morris, Department of Clinical Studies, Veterinary Hospital, University of Pennsylvania, 3850 Spruce St., Philadelphia, PA 19104, USA. E-mail:domorris@vet.upenn.edu Abstract Twenty-one cases of cutaneous vasculitis in small animals (dogs and cats) were reviewed, and cases were divided by clinical signs into five groups. An attempt was made to correlate clinical types of vasculitis with histological inflammatory patterns, response to therapeutic drugs and prognosis. Greater than 50% of the cases were idiopathic, whereas five were induced by rabies vaccine, two were associated with hypersensitivity to beef, one was associated with lymphosarcoma and two were associated with the administration of oral drugs (ivermectin and itraconazole). Only the cases of rabies vaccine-induced vasculitis in dogs had a consistent histological inflammatory pattern (mononuclear/nonleukocytoclastic) and were responsive to combination therapy with prednisone and pentoxifylline, or to prednisone alone. Most cases with neutrophilic or neutrophilic/eosinophilic inflammatory patterns histologically did not respond to pentoxifylline, but responded to sulfone/sulfonamide drugs, prednisone, or a combination of the two. http://www.blackwell-synergy.com/doi...3.2001.00268.x -------------------------------------------------------------------------------- Vitale, Gross, Magro (1999) Vaccine-induced ischemic dermatopathy in the dog Veterinary Dermatology 10 (2), 131–142. doi:10.1046/j.1365-3164.1999.00131.x Prev Article Next Article Full Article Vaccine-induced ischemic dermatopathy in the dog Vitale, Gross & Magro 1Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, California 95616, USA, 2IDDEX Veterinary Services, California Dermatopathology Service, 2825 KOVR Drive, West Sacramento, California 95605, USA, 3Department of Pathology, Beth Israel Hospital, Harvard Medical School, Pathology Services, Inc., 640 Memorial Drive, Cambridge, Massuchusetts 02139, USA Correspondence to: Carlo B. Vitale Present address: Encina Veterinary Hospital, 2803 Ygnacio Valley Road, Walnut Creek, California 94598, USA. Abstract Post-rabies vaccination alopecia associated with concurrent multifocal ischemic dermatopathy was identified in three unrelated dogs. All dogs received subcutaneous rabies vaccine dorsally between the scapulae several months prior to observation of the initial area of alopecia at the vaccination site. All three dogs developed multifocal cutaneous disease within 1–5 months after the appearance of the initial skin lesion. Cutaneous lesions were characterized clinically by variable alopecia, crusting, hyperpigmentation, erosions, and ulcers on the pinnal margins, periocular areas, skin overlying boney prominences, tip of the tail, and paw pads. Lingual erosions and ulcers were observed in two dogs. Histopathologic examination of the skin revealed moderate to severe follicular atrophy, hyalinization of collagen, vasculopathy, and cell-poor interface dermatitis and mural folliculitis. Hypovascularity was demonstrated by diminished Factor VIII staining of blood vessels. Nodular accumulations of lymphocytes, plasma cells, and histiocytes in the deep dermis and panniculus also were noted at the rabies vaccination site. An atrophic, ischemic myopathy paralleling the onset of skin disease was identified in two dogs. Histological examination of muscle biopsy specimens demonstrated perifascicular atrophy, perimysial fibrosis, and complement (C) 5b-9 (membrane attack complex) deposition in the microvasculature of both dogs with myopathy. Marked improvement of the skin disease was obtained with oral pentoxifylline and vitamin E. http://www.blackwell-synergy.com/doi...4.1999.00131.x -------------------------------------------------------------------------------- The Armed Forces Institute of Pathology Department of Veterinary Pathology WEDNESDAY SLIDE CONFERENCE 2002-2003 CONFERENCE 19 26 February 2003 Conference Moderator: Dr. Michael Goldschmidt, MSc, BVMS, MRCVS Diplomate, ACVP Professor, School of Veterinary Medicine University of Pennsylvania Philadelphia, PA 19104-6051 CASE II - 2513-02 (AFIP 2839301) Signalment: 5-year-old, male, castrated, canine, Chihuahua History: One by three cm lesion on the dorso-lateral neck Gross Pathology: None 03WSC19 - 2 - Laboratory Results: None Contributor’s Morphologic Diagnosis: Post-rabies vaccination alopecia with injection site granuloma and panniculitis Contributor’s Comment: The hair follicles are markedly atretic and their lower portions are replaced by an eosinophilic, hyaline stroma. The deeper dermis also has a cleft or seroma pocket that is partially lined by a thin layer of foamy macrophages and multinucleated giant cells with more peripheral lymphoid nodules with many scattered dermal macrophages, lymphocytes and plasma cells. Scattered melanin-laden macrophages (positive with Fontana-Masson melanin stain and negative for hemosiderin with a Prussian blue stain) are in the hyalinized lengths of the hair follicles with a few beneath the epidermal basement membrane (pigmentary incontinence). This is post-rabies vaccination alopecia with an underlying injection site granuloma. Post-rabies vaccination alopecia is most commonly seen in toy or small breeds, especially Poodles, but Chihuahua cases have been reported. The lesion usually develops three to six months after vaccination. Other reports describe mild to severe lymphocytic inflammation with macrophages in the superficial or deep dermis or scattered around hair follicle remnants. The dermis may have smudging of the collagen, especially around the hair follicles. Rabies vaccine antigen has been found in the hair follicle epithelium and in the walls of vessels in the area. One report of focal alopecia developing in all twelve of twelve inbred miniature Poodles injected with a killed rabies vaccine two months earlier suggest that there may be a familial predisposition to this apparently idiosyncratic, hypersensitivity reaction to the antigen. http://www.afip.org/vetpath/WSC/wsc02/02wsc19.pdf CONTINUED ON NEXT POST

02-25-2008, 05:41 AM	#2
Kris Christine YT Addict Join Date: Jan 2008 Location: THE RABIES CHALLENGE FUND Posts: 434	RABIES VACCINE-Skin Pigmentation Reaction Continued This is a continuation of the previous post which was too long. -------------------------------------------------------------------------------- Pentoxifylline (Trental) Pentoxifylline, sold by Hoechst-Roussel under the trade name Trental®, is a methylxanthine derivative that decreases platelet activation, inhibits T- and B-lymphocyte activation, and decreases natural killer cell activity. In humans, it is used for down-regulating inflammatory conditions, such as granuloma anulare, scleroderma, and even spider bites. In veterinary medicine, it is most useful in cases involving some degree of vasculopathy, such as dermatomyositis, vasculitis, rabies vaccine-induced alopecia, and mucinosis. Since it may decease scarring, it is sometimes even used long term in cases of acral lick dermatitis. It is also sometimes used for the treatment of inhalant allergies, allergic bronchitis, and pattern alopecias. With pentoxifylline, it may take 1-3 months before the benefits of treatment are evident. Gastrointestinal upset, either vomiting, diarrhea (or both) is the most likely adverse effect, although thrombocytopenia has also been reported. There have actually been relatively few side effects reported with the drug. Tacrolimus (Protopic) Tacrolimus is an inhibitor of T-lymphocyte activation. It is at least 10 times as potent as cyclosporine, yet is minimally absorbed through the skin. Tacrolimus is available commercially as a 0.1% topical, and as a 0.03% pediatric formulation (Protopic: Fugisawa), in 30 g and 60 g tubes. It is licensed for the treatment of eczematous dermatitis in people. Tacrolimus has been used for the treatment of cutaneous lupus erythematosus, and also for the eczematous manifestations of inhalant allergies. It is typically applied twice daily for a trial period of 6-8 weeks. Once remission is achieved, it may be possible to taper to once daily, and sometimes even alternate-day therapy. There are a few cautions to use, even though major side effects have not been reported. There is some mild to moderate burning at the site of application, at least reported in people. It is important that only a thin film be applied to the skin, and that the product is not ingested. Sun exposure is typically restricted for the first hour or two after application. PENTOXIFYLLINE Pentoxifylline is a methylxanthine derivative first used and marketed in the United States for intermittent claudication in humans. Hypercoagulable states and blood flow abnormalities improve through decreased platelet aggregation and adhesion, increased red cell deformability, decreased vasoconstriction, increased plasminogen activator, increased plasmin, increased antithrombin III, decreased fibrinogen, decreased alpha2-antiplasmin, decreased alpha1-antitrypsin, and decreased alpha2-macroglobulin. Results of subsequent studies revealed that the drug results in a variety of physiologic changes at the cellular level. Immune modulation includes increased leukocyte deformability, decreased leukocyte adhesion and aggregation, decreased neutrophil superoxide release, decreased neutrophil degranulation, increased leukocyte chemotaxis, decreased monocyte TNF-alpha production, decreased leukocyte response to TNF-alpha, decreased production and leukocyte response to IL-1 and IL-12, increased production of IL-10 and PGE2, and decreased natural killer cell activity. Many of these effects result in inhibition of T- and B-cell activation. Wound healing and connective tissue disorders are improved by increased fibroblast collagenases, decreased fibroblast collagen, decreased fibroblast fibronectin, decreased fibroblast glycosaminoglycans, and decreased response to TNF-alpha. Based on these experimental findings, pentoxifylline has been used for a wide variety of diseases in humans. Adverse effects are rare over a wide dosage range, up to 2200 mg/day, and are minimized using sustained-release tablets. Adverse effects include nausea, vomiting, dizziness, and headache, all seen in less than 3% of human patients. Drug interactions have been reported with cisplatin, alkylating agents, and amphotericin B. Cimetidine increases the level of pentoxifylline by decreasing its clearance. Synergistic activity has been reported between pentoxifylline and ciprofloxacin in the inhibition of TNF-alpha. Recent pharmacokinetic studies suggest that pentoxifylline should be administered every 8 hours in dogs and that administration with food does not affect absorption into the systemic circulation. Pentoxifylline has been used for a wide variety of cutaneous disorders in dogs. They include dermatomyositis, vasculitis, rabies vaccine induced vasculitis, vascular thrombosis leading to ear margin necrosis, wounds, acral lick dermatitis, and diseases resulting in severe fibrosis such as deep scarring pyoderma. Variable efficacy has been anecdotally reported for these diseases but no specific cases or controlled studies have been published. Efficacy has been well-documented for the ability of pentoxifylline (Trental, Hoechst Marion Roussel, 10 mg/kg, q12h, PO) to prevent allergic contact reactions to plants of the Commelinceae family in three dogs. Response was seen after only 2 days of treatment with relapse occurring upon discontinuation of the drug in one dog. No adverse effects were observed in the three dogs. A double-blind placebo-controlled study was conducted to evaluate pentoxifylline for the treatment of canine atopic dermatitis. Ten dogs were administered the drug at 10 mg/kg, q12h, PO for 4 weeks. Pruritus and erythema significantly decreased in the dogs administered the test drug versus those on placebo. However, most of the dogs still had residual pruritus at 4 weeks. Increasing the dosage and frequency may increase efficacy. Pentoxifylline is available in 400 mg controlled-release tablets. The optimal dosage and duration of pentoxifylline administration are not known for all of the various indications in dogs. For small dogs, the large tablets are reformulated into capsules. Pentoxifylline causes GI irritancy so should not be reformulated as a liquid and should be administered with a small amount of food.